Showing papers by "Heiner Boeing published in 2011"
Medical Research Council1, Harvard University2, Lund University3, University of Minnesota4, Duke University5, University of Oulu6, Novo Nordisk7, Technische Universität München8, University College London9, University of Lausanne10, University of Eastern Finland11, National University of Singapore12, King's College London13, University of Bristol14, George Washington University15, National Institutes of Health16, University of Bergen17, University of Michigan18, University of North Carolina at Chapel Hill19, University of Groningen20, Utrecht University21, University of Copenhagen22, Erasmus University Rotterdam23, University of Tübingen24, Harokopio University25, Washington University in St. Louis26, University of Maryland, Baltimore27, University of Granada28, Complutense University of Madrid29, University of Turku30, University of Southern Denmark31, Umeå University32, University of Gothenburg33, Laval University34, University of London35, Pennington Biomedical Research Center36, Lille University of Science and Technology37, Newcastle University38, University of Iceland39, Danube University Krems40, Broad Institute41, University of California, Los Angeles42, Hammersmith Hospital43, University of Cambridge44, National Institute for Health and Welfare45
TL;DR: In this paper, a meta-analysis of data from 45 studies of adults and nine studies of children and adolescents was conducted to confirm or refute unambiguously whether physical activity attenuates the association of FTO with obesity risk.
Abstract: Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTOxPA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
447 citations
TL;DR: The MSM website provides a program package that allows nutritional scientists to calculate usual dietary intakes by combining short-term and long-term measurements (multiple sources) and promotes simple access to the MSM to estimate usual food intake for individuals and populations.
Abstract: The Multiple Source Method (MSM) is a new statistical method for estimating usual dietary intake including episodically consumed foods on the basis of two or more short-term measurements such as 24-h dietary recalls. Optional information regarding habitual use or non-use of a food can be included as a covariate in the model estimating the intake, as well as a parameter for identifying consumers and non-consumers. The objective was to implement the MSM algorithms into an easy-to-use statistical program package. The implementation was realized as a web-based application using the Perl application framework Catalyst. As the engine for the statistical calculations, the R system was used. To allow simultaneous use of the program by different users, a multiuser system with a resource bag pattern design was implemented. We established a software program that implements the algorithms of the MSM and allows interactive usage of the method, using standard web technologies. The program is hosted on a website established at the DIFE and can be accessed at https://nugo.dife.de/msm
. The communication between users and the program web site is encrypted, securing transmitted data against unauthorized use. Users can interactively import several data sets, define the analysis model, review and export results and graphs. The use of the program is supported by online help and a user guide. The MSM website provides a program package that allows nutritional scientists to calculate usual dietary intakes by combining short-term and long-term measurements (multiple sources). It promotes simple access to the MSM to estimate usual food intake for individuals and populations.
361 citations
International Agency for Research on Cancer1, Russian Academy2, Nofer Institute of Occupational Medicine3, Curie Institute4, Charles University in Prague5, National and Kapodistrian University of Athens6, Harvard University7, Institut Gustave Roussy8, University of Bremen9, University of Turin10, University of Aberdeen11, University of Padua12, Imperial College London13, Newcastle University14, Glasgow Dental Hospital and School15, National Health Service16, Trinity College, Dublin17, Oswaldo Cruz Foundation18, Universidade Federal de Pelotas19, University of São Paulo20, Catholic University of the Sacred Heart21, University of North Carolina at Chapel Hill22, Pomeranian Medical University23, Fred Hutchinson Cancer Research Center24, Pennsylvania State University25, University of California, Los Angeles26, University of Texas MD Anderson Cancer Center27, Brown University28, Boston University29, University of Minnesota30, University of Pittsburgh31, Maastricht University32, Radboud University Nijmegen33, University of Toronto34, Cancer Care Ontario35, Norwegian University of Science and Technology36, University of Liverpool37, University of Naples Federico II38, University of Cambridge39, University of Oxford40, Utrecht University41, German Cancer Research Center42, Umeå University43, Aarhus University44, University Hospital of North Norway45, University of Tartu46, University of Paris47, New York University48
TL;DR: A genome-wide association study to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
Abstract: Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
308 citations
Centre for Addiction and Mental Health1, Aarhus University2, University of Paris-Sud3, Institut Gustave Roussy4, German Cancer Research Center5, Prevention Institute6, Imperial College London7, Utrecht University8, University of Cambridge9, University of Oxford10, International Agency for Research on Cancer11, Icahn School of Medicine at Mount Sinai12
TL;DR: In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits, which support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.
Abstract: Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.
279 citations
University of Oxford1, Aalborg University2, Aarhus University3, German Cancer Research Center4, National and Kapodistrian University of Athens5, University of Naples Federico II6, Utrecht University7, Basque Government8, Lund University9, Umeå University10, International Agency for Research on Cancer11, University of Cambridge12, Imperial College London13
TL;DR: Results from this large observational study suggest that a higher intake of fruits and vegetables is associated with a reduced risk of IHD mortality.
Abstract: AIMS: A higher intake of fruits and vegetables has been associated with a lower risk of ischaemic heart disease (IHD), but there is some uncertainty about the interpretation of this association. Th ...
261 citations
International Agency for Research on Cancer1, University of Oslo2, Icahn School of Medicine at Mount Sinai3, National and Kapodistrian University of Athens4, European Food Safety Authority5, Aarhus University6, Institut Gustave Roussy7, South University8, Academy of Athens9, Harvard University10, German Cancer Research Center11, University of Naples Federico II12, Imperial College London13, Life Sciences Institute14, Utrecht University15, University Medical Center Utrecht16, Radboud University Nijmegen Medical Centre17, University of Tromsø18, Andalusian School of Public Health19, Basque Government20, Umeå University21, Lund University22, University of Oxford23, University of Cambridge24
TL;DR: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk in this population if study subjects had a greater adherence to Mediterranean dietary patterns.
Abstract: BACKGROUND: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse. METHODS: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142 605 men and 335 873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders. RESULTS: In all, 9669 incident cancers in men and 21 062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio = 0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity) = 0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern. CONCLUSION: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk. British Journal of Cancer (2011) 104, 1493-1499. doi:10.1038/bjc.2011.106 www.bjcancer.com Published online 5 April 2011 (C) 2011 Cancer Research UK
253 citations
TL;DR: This study shows that the MSM is a useful and applicable statistical technique to estimate usual food intake distributions, if at least 2 repeated measurements per participant are available, even for food groups with a sizeable percentage of nonconsumers.
Abstract: Estimating usual food intake distributions from short-term quantitative measurements is critical when occasionally or rarely eaten food groups are considered. To overcome this challenge by statistical modeling, the Multiple Source Method (MSM) was developed in 2006. The MSM provides usual food intake distributions from individual short-term estimates by combining the probability and the amount of consumption with incorporation of covariates into the modeling part. Habitual consumption frequency information may be used in 2 ways: first, to distinguish true nonconsumers from occasional nonconsumers in short-term measurements and second, as a covariate in the statistical model. The MSM is therefore able to calculate estimates for occasional nonconsumers. External information on the proportion of nonconsumers of a food can also be handled by the MSM. As a proof-of-concept, we applied the MSM to a data set from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Calibration Study (2004) comprising 393 participants who completed two 24-h dietary recalls and one FFQ. Usual intake distributions were estimated for 38 food groups with a proportion of nonconsumers > 70 in the 24-h dietary recalls. The intake estimates derived by the MSM corresponded with the observed values such as the group mean. This study shows that the MSM is a useful and applicable statistical technique to estimate usual food intake distributions, if at least 2 repeated measurements per participant are available, even for food groups with a sizeable percentage of nonconsumers. J. Nutr. 141: 914-920, 2011.
250 citations
TL;DR: The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes.
248 citations
National Institutes of Health1, Russian Academy of Sciences2, University of Texas at Austin3, Radboud University Nijmegen Medical Centre4, Nofer Institute of Occupational Medicine5, Charles University in Prague6, Masaryk University7, Palacký University, Olomouc8, Icahn School of Medicine at Mount Sinai9, University of Illinois at Chicago10, Wayne State University11, University of Leeds12, University of Washington13, Imperial College London14, French Institute of Health and Medical Research15, University of Naples Federico II16, Pompeu Fabra University17, University of Cambridge18, University of Oxford19, University of Groningen20, Harvard University21, German Cancer Research Center22, Umeå University23, Aarhus University24, Norwegian University of Science and Technology25, University of Tromsø26, University of Bergen27, Pierre-and-Marie-Curie University28, Institut Gustave Roussy29, Council on Education for Public Health30
TL;DR: A two-stage genome-wide association study of renal cell carcinoma in 3,772 affected individuals and 8,505 controls of European background and followed up 6 SNPs in 3 replication studies reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
Abstract: We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
225 citations
Harvard University1, Academy of Athens2, National and Kapodistrian University of Athens3, International Agency for Research on Cancer4, Max Delbrück Center for Molecular Medicine5, University of Kiel6, Aarhus University7, University of Copenhagen8, South University9, French Institute of Health and Medical Research10, German Cancer Research Center11, University of Naples Federico II12, Utrecht University13, University of Tromsø14, University of Gothenburg15, Lund University16, Umeå University17, University of Cambridge18, Medical Research Council19, University of Oxford20, Icahn School of Medicine at Mount Sinai21
TL;DR: Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections and heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden.
Abstract: Background: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.Methods: ...
215 citations
Utrecht University1, International Agency for Research on Cancer2, University of British Columbia3, Aarhus University4, Aalborg University5, Institut Gustave Roussy6, University of Naples Federico II7, Imperial College London8, German Cancer Research Center9, National and Kapodistrian University of Athens10, Umeå University11, University of Cambridge12, University of Oxford13
TL;DR: Findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer, and the mechanism behind this association needs further elucidation.
Abstract: Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC).
Design Nested case–control study.
Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries.
Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status.
Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy.
Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer.
Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.
University of Southern California1, National Institutes of Health2, Imperial College London3, Science Applications International Corporation4, Harvard University5, American Cancer Society6, University of Oxford7, Institute of Cancer Research8, University of Cambridge9, Cancer Council Victoria10, University of Melbourne11, University of Bristol12, University of Warwick13, Karolinska Institutet14, Johns Hopkins University15, Wake Forest University16, Washington University in St. Louis17, University of Colorado Boulder18, VA Boston Healthcare System19, International Agency for Research on Cancer20, Umeå University21, University of Hawaii22, Technical University of Denmark23, New York University24, Kaiser Permanente25
TL;DR: The authors conducted a GWAS in 2782 advanced prostate cancer cases and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs) and identified a new susceptibility locus associated with overall prostate cancer risk at 2q37.
Abstract: Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade >= 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 x 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P = 0.72 and P = 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
Medical Research Council1, Lund University2, Wellcome Trust Sanger Institute3, University of Naples Federico II4, Charité5, Utrecht University6, University of Paris-Sud7, University of Oxford8, Imperial College London9, International Agency for Research on Cancer10, Umeå University11, Novo Nordisk12, University of Cambridge13, German Cancer Research Center14, University of Helsinki15, Wageningen University and Research Centre16
TL;DR: A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39–1.64) for a 10 year age difference, adjusted for sex.
Abstract: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.
TL;DR: The four methods that were compared seem to provide good estimates of the usual intake distribution of nutrients, but care needs to be taken when a nutrient has a high within-person variation or has a highly skewed distribution, and when the sample size is small.
Abstract: The aim of this paper was to compare methods to estimate usual intake distributions of nutrients and foods. As ‘true’ usual intake distributions are not known in practice, the comparison was carried out through a simulation study, as well as empirically, by application to data from the European Food Consumption Validation (EFCOVAL) Study in which two 24-h dietary recalls (24-HDRs) and food frequency data were collected. The methods being compared were the Iowa State University Method (ISU), National Cancer Institute Method (NCI), Multiple Source Method (MSM) and Statistical Program for Age-adjusted Dietary Assessment (SPADE). Simulation data were constructed with varying numbers of subjects (n), different values for the Box–Cox transformation parameter (λBC) and different values for the ratio of the within- and between-person variance (rvar). All data were analyzed with the four different methods and the estimated usual mean intake and selected percentiles were obtained. Moreover, the 2-day within-person mean was estimated as an additional ‘method’. These five methods were compared in terms of the mean bias, which was calculated as the mean of the differences between the estimated value and the known true value. The application of data from the EFCOVAL Project included calculations of nutrients (that is, protein, potassium, protein density) and foods (that is, vegetables, fruit and fish). Overall, the mean bias of the ISU, NCI, MSM and SPADE Methods was small. However, for all methods, the mean bias and the variation of the bias increased with smaller sample size, higher variance ratios and with more pronounced departures from normality. Serious mean bias (especially in the 95th percentile) was seen using the NCI Method when rvar=9, λBC=0 and n=1000. The ISU Method and MSM showed a somewhat higher s.d. of the bias compared with NCI and SPADE Methods, indicating a larger method uncertainty. Furthermore, whereas the ISU, NCI and SPADE Methods produced unimodal density functions by definition, MSM produced distributions with ‘peaks’, when sample size was small, because of the fact that the population's usual intake distribution was based on estimated individual usual intakes. The application to the EFCOVAL data showed that all estimates of the percentiles and mean were within 5% of each other for the three nutrients analyzed. For vegetables, fruit and fish, the differences were larger than that for nutrients, but overall the sample mean was estimated reasonably. The four methods that were compared seem to provide good estimates of the usual intake distribution of nutrients. Nevertheless, care needs to be taken when a nutrient has a high within-person variation or has a highly skewed distribution, and when the sample size is small. As the methods offer different features, practical reasons may exist to prefer one method over the other.
TL;DR: The data show an increase in obesity prevalence since the 1990ies, and predictions by 2015 suggests a sizeable further increase in European populations, however, the estimates from the leveling off model were considerably lower.
Abstract: Objective
To investigate trends in obesity prevalence in recent years and to predict the obesity prevalence in 2015 in European populations.
Methods
Data of 97 942 participants from seven cohorts involved in the European Prospective Investigation into Cancer and Nutrition (EPIC) study participating in the Diogenes project (named as “Diogenes cohort” in the following) with weight measurements at baseline and follow-up were used to predict future obesity prevalence with logistic linear and non-linear (leveling off) regression models. In addition, linear and leveling off models were fitted to the EPIC-Potsdam dataset with five weight measures during the observation period to find out which of these two models might provide the more realistic prediction.
Results
During a mean follow-up period of 6 years, the obesity prevalence in the Diogenes cohort increased from 13% to 17%. The linear prediction model predicted an overall obesity prevalence of about 30% in 2015, whereas the leveling off model predicted a prevalence of about 20%. In the EPIC-Potsdam cohort, the shape of obesity trend favors a leveling off model among men (R2 = 0.98), and a linear model among women (R2 = 0.99).
Conclusion
Our data show an increase in obesity prevalence since the 1990ies, and predictions by 2015 suggests a sizeable further increase in European populations. However, the estimates from the leveling off model were considerably lower.
University of Groningen1, Imperial College London2, Aarhus University3, French Institute of Health and Medical Research4, University of Naples Federico II5, German Cancer Research Center6, National and Kapodistrian University of Athens7, Pompeu Fabra University8, Umeå University9, University of Cambridge10, University of Oxford11
TL;DR: Simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions.
Abstract: Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions.
Cambridge University Hospitals NHS Foundation Trust1, Utrecht University2, International Agency for Research on Cancer3, Imperial College London4, German Cancer Research Center5, Institut Gustave Roussy6, Aarhus University7, Aalborg University8, University of Oxford9, National and Kapodistrian University of Athens10, Lund University11, University of Tromsø12, University of Turin13, University of Naples Federico II14
TL;DR: It is suggested that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.
TL;DR: Serum reliability of metabolites over a 4-month period was good, and for most of the metabolites a single measurement may be sufficient for risk assessment in epidemiologic studies with healthy subjects.
Abstract: Metabolomics is a promising tool for discovery of novel biomarkers of chronic disease risk in prospective epidemiologic studies. We investigated the between- and within-person variation of the concentrations of 163 serum metabolites over a period of 4 months to evaluate the metabolite reliability expressed by the intraclass-correlation coefficient (ICC: the ratio of between-person variance and total variance). The analyses were performed with the BIOCRATES AbsoluteIDQ™ targeted metabolomics technology, including acylcarnitines, amino acids, glycerophospholipids, sphingolipids and hexose in 100 healthy individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who had provided two fasting blood samples 4 months apart. Overall, serum reliability of metabolites over a 4-month period was good. The median ICC of the 163 metabolites was 0.57. The highest ICC was observed for hydroxysphingomyelin C14:1 (ICC = 0.85) and the lowest was found for acylcarnitine C3:1 (ICC = 0). Reliability was high for hexose (ICC = 0.76), sphingolipids (median ICC = 0.66; range: 0.24–0.85), amino acids (median ICC = 0.58; range: 0.41–0.72) and glycerophospholipids (median ICC = 0.58; range: 0.03–0.81). Among acylcarnitines, reliability of short and medium chain saturated compounds was good to excellent (ICC range: 0.50–0.81). Serum reliability was lower for most hydroxyacylcarnitines and monounsaturated acylcarnitines (ICC range: 0.11–0.45 and 0.00–0.63, respectively). For most of the metabolites a single measurement may be sufficient for risk assessment in epidemiologic studies with healthy subjects.
International Agency for Research on Cancer1, German Cancer Research Center2, University of Naples Federico II3, University of Oxford4, University of Tromsø5, National and Kapodistrian University of Athens6, Utrecht University7, Imperial College London8, University of Cambridge9, Medical Research Council10, Umeå University11, Lund University12, Institut Gustave Roussy13, South University14
TL;DR: Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity and various lifestyle factors throughout Europe, with some geographical variability in their food sources.
Abstract: Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19.83 (SE 1.53) mg/d (Bilthoven, The Netherlands) to 64.88 (SE 1.86) mg/d (Turin, Italy), whereas for women the range was 18.73 (SE 2.80) mg/d (Granada, Spain) to 44.08 (SE 2.45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources.
TL;DR: Higher fruit and dairy products consumption was associated with a lower gain in WCBMI whereas the consumption of white bread, processed meat, margarine, and soft drinks was positively associated with ΔWCBMI.
Abstract: Background: Dietary factors such as low energy density and low glycemic index were associated with a lower gain in abdominal adiposity. A better understanding of which food groups/items contribute to these associations is necessary. Objective: To ascertain the association of food groups/items consumption on prospective annual changes in "waist circumference for a given BMI" (WC(BMI)), a proxy for abdominal adiposity. Design: We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC(BMI) was defined as the residuals of waist circumference regressed on BMI, and annual change in WC(BMI) (Delta WC(BMI), cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between food groups/items and Delta WC(BMI) was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Results: Higher fruit and dairy products consumption was associated with a lower gain in WC(BMI) whereas the consumption of white bread, processed meat, margarine, and soft drinks was positively associated with Delta WC(BMI). When these six food groups/items were analyzed in combination using a summary score, those in the highest quartile of the score - indicating a more favourable dietary pattern - showed a Delta WC(BMI) of -0.11 (95% CI -0.09 to -0.14) cm/y compared to those in the lowest quartile. Conclusion: A dietary pattern high in fruit and dairy and low in white bread, processed meat, margarine, and soft drinks may help to prevent abdominal fat accumulation.
French Institute of Health and Medical Research1, University of Naples Federico II2, University of Cambridge3, University of Oxford4, Utrecht University5, Radboud University Nijmegen6, National and Kapodistrian University of Athens7, German Cancer Research Center8, University of Gothenburg9, Umeå University10, Aarhus University11, University of Tromsø12, International Agency for Research on Cancer13, Imperial College London14
TL;DR: Heavy consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort, and associations were primarily observed at the highest amounts of drinking in men.
German Cancer Research Center1, Leipzig University2, International Agency for Research on Cancer3, Aarhus University4, South University5, Harvard University6, University of Naples Federico II7, Basque Government8, Utrecht University9, University of Cambridge10, Medical Research Council11, University of Oxford12, Imperial College London13
TL;DR: Further research is needed to establish through which molecular pathways, and during which evolutionary stages of development, androgens and estrogens can promote the occurrence of both receptor-positive and -negative clinical breast tumors.
Abstract: Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of hormone receptor [estrogen receptor (ER) and/or progesterone receptor (PR)] defined breast cancer. In a case-control study nested within the EPIC cohort (European Prospective Investigation into Cancer and Nutrition), estradiol, testosterone, and sex hormone-binding globulin levels were measured in prediagnostic serum samples from postmenopausal women not using hormone replacement therapy at blood donation. A total of 554 women who developed invasive breast cancer with information on receptor status were matched with 821 control subjects. Conditional logistic regression models estimated breast cancer risk with hormone concentrations according to hormone receptor status of the tumor. Sex steroid hormones were associated with risks of not only ER+PR+ breast cancer [estradiol OR for highest vs. lowest tertile = 2.91 (95% CI: 1.62-5.23), P(trend) = 0.002; testosterone OR = 2.27 (95% CI: 1.35-3.81), P(trend) = 0.002] but also of ER-PR- breast cancer [estradiol OR = 2.11 (95% CI: 1.00-4.46), P(trend) = 0.05; testosterone OR = 2.06 (95% CI: 0.95-4.46), P(trend) = 0.03], with associations appearing somewhat stronger in the receptor-positive disease. Serum androgens and estrogens are associated with risks of both hormone receptor-negative as well as receptor-positive breast tumors. Further research is needed to establish through which molecular pathways, and during which evolutionary stages of development, androgens and estrogens can promote the occurrence of both receptor-positive and -negative clinical breast tumors.
German Cancer Research Center1, University of Zurich2, University of Freiburg3, Aarhus University4, South University5, University of Paris-Sud6, Leipzig University7, National and Kapodistrian University of Athens8, Harvard University9, Academy of Athens10, Imperial College London11, University of Naples Federico II12, Utrecht University13, Umeå University14, Karolinska Institutet15, University of Gothenburg16, Lund University17, University of Cambridge18, Medical Research Council19, University of Oxford20, International Agency for Research on Cancer21, Brown University22
TL;DR: The data on HbA1c show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in Hb a1c levels, relatively independently of obesity and insulin resistance—the classic and major risk factors for type 2 diabetes.
Abstract: Aims/hypothesis
There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.
International Agency for Research on Cancer1, University of Naples Federico II2, Lund University3, National and Kapodistrian University of Athens4, University of Tromsø5, University of East Anglia6, Aarhus University7, Imperial College London8, Utrecht University9, Umeå University10, University of Oxford11, German Cancer Research Center12, Institut Gustave Roussy13, University of Cambridge14, Medical Research Council15
TL;DR: Heterogeneity in intake of these three sub-classes of flavonoids across European regions is shown and highlights differences by sex and other sociodemographic and lifestyle factors.
Abstract: Flavonols, flavanones and flavones (FLAV) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo. We aimed to estimate the FLAV dietary intake, their food sources and associated lifestyle factors in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. FLAV intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven study centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer databases and was expanded using recipes, estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall. Our results showed that the highest FLAV-consuming centre was the UK health-conscious group, with 130·9 and 97·0 mg/d for men and women, respectively. The lowest FLAV intakes were 36·8 mg/d in men from Umea and 37·2 mg/d in women from Malmo (Sweden). The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46·6 to 52·9 % depending on the region. Flavonols ranged from 38·5 to 47·3 % and flavones from 5·8 to 8·6 %. FLAV intake was higher in women, non-smokers, increased with level of education and physical activity. The major food sources were citrus fruits and citrus-based juices (especially for flavanones), tea, wine, other fruits and some vegetables. We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors.
TL;DR: Associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus and mortality showed the strongest association.
Abstract: Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.
German Cancer Research Center1, Aalborg University2, Aarhus University3, Andalusian School of Public Health4, Basque Government5, University of Cambridge6, Medical Research Council7, University of Oxford8, Harvard University9, National and Kapodistrian University of Athens10, Academy of Athens11, Umeå University12, International Agency for Research on Cancer13, Imperial College London14
TL;DR: An association with prostate cancer risk is found for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
Abstract: The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p,0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78– 0.94, p = 1.3610 23 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.6610 24 for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
Cancer Epidemiology Unit1, Aarhus University2, Aalborg University3, Aarhus University Hospital4, German Cancer Research Center5, National and Kapodistrian University of Athens6, Harvard University7, Academy of Athens8, French Institute of Health and Medical Research9, Prevention Institute10, Utrecht University11, Imperial College London12, University of Tromsø13, Basque Government14, University of Cambridge15, International Agency for Research on Cancer16
TL;DR: Height and BMI are associated with IGF-I and its binding proteins, which may be mechanisms through which body size contributes to increased risk of several cancers.
Abstract: Background: Height and BMI are risk factors for several types of cancer and may be related to circulating concentrations of insulin-like growth factor-I (IGF-I), a peptide associated with increased cancer risk.Aim: To assess the associations between height, BMI and serum concentrations of IGF-I and IGF binding protein (IGFBP)-1, -2 and -3.Subjects and methods: This cross-sectional analysis included 1142 men and 3589 women aged 32–77 years from the multi-centre study, the European Prospective Investigation of Cancer and Nutrition (EPIC).Results: In men, there was a positive association between height and IGF-I; each 10 cm increment in height was associated with an increase in IGF-I concentrations of 4.3% (95% confidence interval (CI): 1.3–7.5%, p for trend = 0.005), but this association was not statistically significant for women (0.9%, 95% CI: − 0.7 to 2.6%, p for trend = 0.264). In both men and women, the association between IGF-I and BMI was non-linear and those with a BMI of 26–27 kg/m2 had the highest...
International Agency for Research on Cancer1, University of Bristol2, Newcastle University3, University of Bergen4, Institut Gustave Roussy5, French Institute of Health and Medical Research6, South University7, German Cancer Research Center8, Utrecht University9, Imperial College London10, University of Cambridge11, University of Oxford12, University of Naples Federico II13, National and Kapodistrian University of Athens14, Academy of Athens15, Harvard University16, Umeå University17
TL;DR: The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinines and lung cancer that require further investigation.
Abstract: BACKGROUNDS: Multiple polymorphisms affecting smoking behavior have been identified through genome-wide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels. METHODS: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13. RESULTS: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk. CONCLUSIONS: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation. IMPACT: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior.
Utrecht University1, University of Tromsø2, Aarhus University3, French Institute of Health and Medical Research4, University of Turin5, University of Naples Federico II6, German Cancer Research Center7, National and Kapodistrian University of Athens8, Academy of Athens9, Harvard University10, Lund University11, Umeå University12, University of Cambridge13, Medical Research Council14, University of Oxford15, International Agency for Research on Cancer16, Imperial College London17
TL;DR: Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.
International Agency for Research on Cancer1, Aarhus University2, South University3, Institut Gustave Roussy4, German Cancer Research Center5, National and Kapodistrian University of Athens6, University of Turin7, University of Naples Federico II8, Prevention Institute9, University of Tromsø10, University Medical Center Utrecht11, Utrecht University12, Andalusian School of Public Health13, Umeå University14, Lund University15, University of Oxford16, University of Cambridge17, Imperial College London18
TL;DR: In this article, the authors combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples.